This application A Longitudinal MRI Study of Brain Development in Fragile X Syndrome, is a proposal to conduct a longitudinal MRI study of very early brain and behavior development at 6, 12 and 24 months in infants with Fragile X Syndrome (FXS). This study will examine how the trajectory and growth of brain development in infants with FXS compares to early brain development in infants (at high-risk for autism) who later develop an autism spectrum disorder and in infants with typical brain development. Since many children with FXS also have an autism spectrum disorder (ASD), the design of this study will allow us to contrast brain development profiles in ASD children without FXS, as well as those FXS children who may also have an ASD. The high-risk autism subjects and typical controls are being collected as part of a funded Autism Centers of Excellence (ACE) Network entitled, A Longitudinal MRI Study of Infants at Risk for Autism, currently in year 2. Three of the ACE Network sites will be participating in this project (two clinical data collection sites: UNC and Washington University, and a data coordinating site at Montreal Neurological Institute). Resources in this network, and available to this proposal, include expertise in imaging methods for infant brain and behavioral tools for detecting early (emerging) signs of autism. The final sample of FXS in this study will include 37 infants with FXS (with either 2 or 3 longitudinal scans each). For data analysis in this current proposal, the infants with FXS will be compared to the ACE dataset of 68 infants with ASD (without FXS), 163 infants at risk for ASD but considered ASD(-), and 66 TYP controls. Analysis will examine longitudinal MRI and behavioral data at 6, 12 and 24 months for these children. Preliminary data from our group suggests that the brain volume profiles of FXS and autistic children are significantly different at age 2. Individuals with FXS show a pattern of brain abnormalities at age 2 that differs from typical and developmentally-delayed (non-FXS) two year olds (with marked temporal lobe white matter enlargement, and ~40% caudate enlargement), and autistic two year olds with FXS differ strikingly from autistic non-FXS two year olds. By contrasting the early brain development of infants with FXS, we will be able to address several important hypotheses about the trajectory of early post- natal brain overgrowth (regions, tissues, structures and fiber tracts) in FXS, as measured on MRI and DTI, and its potential relationship to clinical features, particularly those features characteristic of and associated with ASD. This study has the potential to distinguish specific behavioral, genetic, and neurobiological features that characterize infants with FXS in comparison to infants at risk for autism without FXS and those with typical development. This proposal is a response to RFA PA-07-284 that requests submissions examining the interface of autism and Fragile X Syndrome. PUBLIC HEALTH RELEVANCE: A Longitudinal MRI Study of Brain Development in Fragile X Syndrome, is a proposal to study very early brain and behavior development at 6, 12 and 24 months in infants with Fragile X Syndrome (FXS) using Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI). We will examine how the trajectory and growth of brain development in infants with FXS compares to early brain development in infants at high-risk for autism (who later develop an autism spectrum disorder), as well as typical developing infants. We will address several important hypotheses about the trajectory of early post-natal brain overgrowth (regions, tissues, structures and fiber tracts) in FXS, as measured on MRI and DTI, and its potential relationship to clinical features, particularly those features characteristic of ASD. This study has the potential to distinguish specific behavioral, genetic, and neurobiological features that characterize infants with FXS in comparison with infants at high-risk for autism and those with typical development.